Low affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) (CD16a)

Low affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa), also known as CD16a, is a cluster of differentiation molecule found on the surface of natural killer (NK) cells, monocytes, and macrophages. It serves as a key mediator of antibody-dependent cellular cytotoxicity (ADCC), a process where the immune system targets and kills cells coated with IgG antibodies [1]. When the Fc region of an antibody bound to a target cell engages FcγRIIIa, it triggers an intracellular signaling cascade involving the immunoreceptor tyrosine-based activation motif (ITAM), leading to the release of perforins and granzymes [2]. This mechanism is central to the efficacy of many therapeutic monoclonal antibodies used in oncology, such as rituximab and trastuzumab [3]. In the context of untransduced NK (UTD-NK) cells, the therapeutic effect relies on the endogenous expression of this receptor to recognize and eliminate opsonized tumor cells [4]. Genetic variations in the FCGR3A gene, particularly the V158F polymorphism, can significantly influence the binding affinity of antibodies and the subsequent clinical response to immunotherapy [5]. Therapeutic strategies often involve engineering antibodies with enhanced Fc-binding affinity to FcγRIIIa or using NK cell products that highly express specific variants of the receptor to improve clinical efficacy [6].

Other names

FCGR3AFc-gamma RIIIaCD16A antigenIgG Fc receptor III-AFcR-10

Binding of the Fc region of an IgG antibody (opsonized on a target cell) to the FcγRIIIa receptor on effector cells like NK cells, triggering ITAM-mediated signaling and the release of cytotoxic granules and proinflammatory cytokines to lyse the target cell.